艾滋病与临床研究杂志

Plasma Tenofovir Concentrations and Proximal Tubular Dysfunction in HIV-Infected Adults Receiving Tenofovir in Thailand

Abstract

Anchalee Avihingsanon, Jiratchaya Sophonphan, Narukjaporn Thammajaruk, Prachya Chaihong, David Burger, Tim R Cressey, Reshmie A Ramautarsing, Kearkiat Praditornsilpa, Yingyos Avihingsanon, Kiat Ruxrungtham and HIV-NAT 114 study team

Background: HIV-infected Asians may be at risk for tenofovir toxicity due to their relatively low body weight (BW). We assessed the prevalence of proximal tubular dysfunction (PRTD) and risk associated with PRTD in HIV-infected adults receiving tenofovir in Thailand.

Methods: A cross-sectional study in HIV-infected adults (≥ 18years) treated with tenofovir for >1 year. Twenty-fourhour urine samples were collected to assess PRTD. PRTD was defined as the presence of >2 of the following criteria: hyper-phosphaturia (total excretion of phosphate >1200 mg/day or renal tubular reabsorption of phosphate (TmP/ GFR) < 2.6 mg/dl), hyper-uricosuria (FE of uric acid >15%), or non-diabetic glucosuria. Mid-dose tenofovir plasma concentrations were determined and concentrations >160 ng/mL were used as a cut-off for assessing risk of PRTD.

Results: 351 subjects (52% males) with median age of 40.2 years, BW of 58.9 kg, and duration of tenofovir treatment 4.7 years were included. 93% had a HIV-1 RNA <50 copies/mL and 7% were co-infected with HCV. Fiftyfour (15.4%) patients were diagnosed with PRTD. In a multivariate analysis, only a mid-dose tenofovir concentration >160ng/mL was associated with PRTD [odds ratio: OR 2.02 (95% CI 1.13-3.66)]; 32 of 54 (59.2%) with PRTD had a tenofovir concentration >160 ng/ml; versus 124 of 297 patients (41.7%) without PRTD (p = 0.02). Predictors of a tenofovir concentration >160ng/mL were BW<55 kg [OR2.32 (95% CI 1.45-3.68)], chronic HCV [OR 2.64 (95% CI 1.13-6.17)], eGFR<90 mL/min/1.73m2 [OR 2.66 (95% CI 1.64-4.31)], lopinavir/ritonavir [OR 2.47 (95% CI 1.32-4.6)] and PRTD [OR 2.08(95% CI 1.10-3.92)].

Conclusion: Mid-dose tenofovir concentrations >160 ng/mL were independently associated with PRTD. Tubular function should be closely monitored in patients using tenofovir with BW<55 kg, lopinavir/ritonavir use, chronic hepatitis C, or low eGFR.